Neurogenesis in the central nervous system of adult vertebrates is a remarkable occurrence with obvious health-related implications. One forebrain nucleus that promises to provide significant data toward understanding the process of adult neurogenesis is the hyperstriatum ventrale, pars caudale (HVc) in canaries. New neurons in this nucleus are born at relatively high rates (1-2% of HVc's total per day) within a ventricular zone adjacent to HVc. The specific aims of the present proposal are to understand the normal processes of neuronal birth, migration, and maturation of these newly formed neurons into existing neural circuits. Newly formed neurons will be identified with tritiated (3H)-thymidine autoradiographic birth dating. The ultrastructural changes that take place in these neurons from birth to maturation and possibly death will be characterized by examining labeled cells in the HVc at various survival times after 3H-thymidine administration. Neuronal identities of labeled cells at these survival times will be further confirmed by combining 3H-thymidine autoradiography with immunocytochemistry for substances that are present specifically in glial cells or neurons. Kainic acid injections into the ventral portion of HVc will be used to test the hypothesis that cell death can stimlulate an increase in the rate of neurogenesis. Antisera to substances thought to be related to neuronal migration and neurite outgrowth will also be tested on HVc neurons. Immunocytochemical techniques will be used to locate putative neurotransmitters and peptides within HVc neurons, and when combined with 3H-thymidine autoradiography, will be used to locate these substances within the new neurons. The purpose of this investigation is to identify what special features are present in the HVc of the canary song system that enable this remarkable neuroplasticity to take place. The ultimate goal to is to achieve neurogenesis in the adult human in order to manipulate regions of the CNS affected by degenerative disorders or trauma.